NITRIC-OXIDE AND VENTILATORY RESPONSE TO HYPOXIA

被引:69
作者
HAXHIU, MA
CHANG, CH
DRESHAJ, IA
EROKWU, B
PRABHAKAR, NR
CHERNIACK, NS
机构
[1] CASE WESTERN RESERVE UNIV,SCH MED,DEPT PEDIAT,CLEVELAND,OH 44106
[2] CASE WESTERN RESERVE UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,CLEVELAND,OH 44106
来源
RESPIRATION PHYSIOLOGY | 1995年 / 101卷 / 03期
关键词
CONTROL OF BREATHING; (CENTRAL HYPOXIA); HYPOXIA; (CENTRAL MEDIATORS); MAMMALS; (RAT); MEDIATORS; (NITRIC OXIDE; CNS HYPOXIA);
D O I
10.1016/0034-5687(95)00020-E
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
It is believed that hypoxia results in the release of neurotransmitters in the central nervous system, which can excite or inhibit breathing. Recent evidence indicates that nitric oxide (NO) is a physiological messenger molecule that may serve as a neurotransmitter in the CNS. In this study we examined (1) the localization of nitric oxide synthase (NOS) within the nucleus tractus solitarius, and (2) the role of the NO-cGMP pathway in the respiratory response to oxygen deprivation. Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry was used to determine the distribution of neurons that express NOS, an enzyme involved in NO formation. The NOS inhibitor N-omega-nitro-L-arginine was used as tool to assess the NOS activity in the medulla, and to define the role of NO in the respiratory response to acute oxygen deprivation. In the rat and the cat brainstem, histochemical studies showed the presence of NADPH-diaphorase reactive neurons within subnuclei of the nucleus tractus solitarius which receive peripheral chemoreceptor inputs. Chronic pretreatment of rats with N-omega-nitro-L-arginine (75 mg/kg, ip, twice daily for 7 days) caused a significant decrease in cGMP, and attenuated the ventilatory response to hypoxia. In anesthetized, paralyzed, vagotomized and artificially ventilated cats with intact carotid sinus nerves (n = 8), administration of N-omega-nitro-L-arginine (30-100 mg/kg) attenuated the response to hypoxia, and caused the hypoxia induced roll-off of phrenic nerve activity to occur significantly earlier than when NOS activity was not inhibited. In sinoaortic denervated cats (n = 9) blockage of NOS potentiated the decline of the phrenic nerve output. The data suggest that oxygen deprivation leads to activation of NO-cGMP pathway in the central nervous system, which contributes to the induction and maintenance of hypoxia-induced increase in respiratory output. In addition, these findings indicate that NO may inhibit inhibitory synaptic transmission that is triggered by CNS hypoxia, and this is not directly related to peripheral chemoreceptor inputs.
引用
收藏
页码:257 / 266
页数:10
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